The long-range objective of this research is to elucidate the number, function and regulation of the histocompatibility-linked immune response (Ir) genes and the nature of their products. We have recently produced in the mouse antisera reactive with cell-surface antigens on T- lymphocytes which are controlled by the I-region of the H-2 gene complex. The immediate objectives of the proposed research are to better define these new Ia antigens (I region-associated) and to determine their relationship, if any, to Ir gene products and to mechanisms of immune response. The specific aims of this research are: 1) to more thoroughly define the genetic and serological variation of the Ia antigens; 2) to better define the cellular and tissue distribution of the Ia antigens, especially of T-lymphocytes, and their relationship to other alloantigens on lymphocyte surfaces; 3) to define the chemical nature of the Ia antigens; and 4) to determine whether Ia antigens play a role in immunologic functions by testing the capacity of anti-Ia sera to block in vitro immune responses, in vitro stimulation of lymphocytes by specific antigens, or the mixed leucocyte reaction or cell-mediated lymphocytotoxicity.